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Title: [Effect of Connexin on Cochlear Blood-Labyrinth Barrier in a Mouse Model of Endolymphatic Hydrops]. Author: Chen JH, Jiang Y, Zhou L, Long LL, Tang YD. Journal: Sichuan Da Xue Xue Bao Yi Xue Ban; 2022 Mar; 53(2):291-296. PubMed ID: 35332732. Abstract: OBJECTIVE: To examine the expression of tight-junction connexin ZO-1 in the stria vascularis tissue of the cochlea by using spontaneous endolymphatic hydrops animal model constructed with PHEX gene mutant mice, and to analyze the dynamic changes of the gene mutant mice in pathology, imaging, and hearing function. METHODS: Male Hyp-Duk/Y mice with PHEX gene mutation were selected as the experimental group at three time points, 21 days post birth (P21), 90 days post birth (P90) and 120 days post birth (P120), and wild-type male mice of the same ages were selected as the control groups. The cochlear sections were HE-stained in order to observe whether endolymphatic hydrops was present or absent and to assess its severity. The expression of connexin ZO-1 in both groups was evaluated through immunohistochemical staining of cochlear sections. Auditory-evoked brainstem response (ABR) was induced in both groups at P90 and gadolinium-enhanced MRI was conducted in vivo to observe the middle-order endolymphatic dilatation of cochlea in experimental and control mice aged P21, P90 and P120. RESULTS: HE staining of pathological sections of PHEX Hyp-Duk/Y mice aged P90 and P120 showed increased endolymphatic hydronephrosis. The level of striae ZO-1 in PHEX Hyp-Duk/Y mice aged P90 and P120 was significantly lower than that of the controls of the same age (P<0.05). The expression level of ZO-1 was significantly negatively correlated with the degree of endolymphatic hydronephrosis (r=-0.939, P<0.01). The bilateral ABR threshold of PHEX Hyp-Duk/Y mice aged P90 was higher than that of the wild-type mice of the same age, and the mutant mice showed asymmetric hearing loss on both sides. Severe endolymphatic hydronephrosis was observed in PHEX Hyp-Duk/Y mice aged P90 and P120 through in vivo MRI gadolinium imaging. CONCLUSION: PHEX Hyp-Duk/Y can be used as a sound model for basic research of Ménière's disease. Compared with wild-type mice, PHEX Hyp-Duk/Y mice showed decreased expression of connexin protein ZO-1, which damaged the function of the blood-labyrinth barrier in stria vascularis, and was involved in the formation of endolymphatic hydrops. 7.0 T MRI gadolinium imaging can be used to observe the changes of severe endolymphatic hydrops in mice in vivo, providing imaging basis for the diagnosis of Ménière's disease. 目的: 本研究拟采用自发性膜迷路积水动物模型PHEX基因突变小鼠研究紧密连接蛋白ZO-1在耳蜗血管纹组织中的表达,分析突变体小鼠在病理学、影像学及听力功能上的动态改变。 方法: 选取出生后21 d(P21)、出生后90 d(P90)、出生后120 d(P120)的PHEX基因突变的Hyp-Duk/Y雄性小鼠为实验组,同龄的野生型雄性小鼠为对照组,耳蜗切片HE染色观察有无膜迷路积水表现并评估严重程度,取耳蜗行免疫组化染色评估紧密连接蛋白ZO-1的表达;两组均在P90时检测听觉诱发脑干反应(auditory-evoked brainstem response, ABR),在P21、P90、P120行7.0 T MRI钆造影活体观察耳蜗中阶内淋巴扩张情况。 结果: P90、P120的实验组小鼠病理切片HE染色可见膜迷路积水,血管纹ZO-1水平较同龄对照组降低,差异有统计学意义(P<0.05)。ZO-1表达水平与膜迷路积水程度呈明显负相关(r=−0.939,P<0.01)。P90的实验组小鼠双侧ABR阈值较同日龄对照组升高,实验组小鼠双侧呈不对称性听力下降。P90、P120的实验组小鼠通过MRI钆造影可活体观察到重度膜迷路积水改变。 结论: PHEX Hyp-Duk/Y可作为梅尼埃病基础研究的良好模型。PHEX Hyp-Duk/Y小鼠发生膜迷路积水的机制与紧密连接蛋白ZO-1表达水平下降导致血管纹血迷路屏障功能破坏有关。7.0 T MRI钆造影可活体观察小鼠重度膜迷路积水改变,为梅尼埃病的诊断提供影像学依据。[Abstract] [Full Text] [Related] [New Search]